Construction,Diagnosis And Therapy Performance Of Two Kinds Rare-Earth Upconversion Multi-Functional Nanoplatforms In Tumor Hypoxia

Cancer,one of the leading causes of death worldwide,is a major disease which seriously endangers human health.In recent years,nanocomposites based on rare earth upconversion nanomaterials have achieved great advantages in the treatment of tumors and multimodal imaging.Due to the inherent special anti-Stokes fluorescence properties,rare earth upconversion materials can convert near-infrared light(700-1400 nm)into visible light or ultraviolet light.When combined with a photosensitizer,UV/visible light light-based optical therapy and diagnosis can be realized.Tumor hypoxia is one of the salient features of the tumor microenvironment,and is the main reason for the poor efficacy of phototherapy and chemotherapy.Based on this characteristic,the main research purpose of this paper is to design and synthesize nanomaterials that respond specifically to the hypoxic acid environment of tumors using rare earth upconversion nanoparticles as carriers,to achieve efficient diagnosis and treatment while reducing side effects.The specific research contents are as follows:A mesoporous core-shell nano-catalyst with acidic response in tumor microenvironment was synthesized by high-temperature pyrolysis.By the way of coating mesoporous cerium oxide(mCeO_x)around the upconversion nanoparticles(UCNPs,NaGdF₄:Yb,Tm@NaGdF₄)and activated by 980 nm near-infrared laser,cerium oxide as an inorganic material with catalase properties can be reversibly converted from Ce⁴⁺to Ce³⁺and catalyze the H₂O₂ into H₂O and O₂ at the same time,thus achieving the oxygen-compensated photodynamic therapy.Long-wavelength near-infrared lasers own large penetration depth and low phototoxicity to biological tissues.And the core-inert shell structured UCNPs could efficiently convert the NIR photons into ultraviolet(UV)light,which can further trigger Ce O_x to produce reactive oxygen species(ROS)for therapy.Moreover,the mesoporous strcture of UCNPs@mCeO_xwas ideal for storing chemotherapeutic doxorubicin(DOX)(store rate:47.52%).The adequate O₂ played a key role in relieving drug fastness via chemotherapy in hypoxic tumors,which strengthened the synergy between PDT and chemotherapy and presented the excellent antitumor property.A Fe-Mn-doped layered double hydroxide(FeMn-LDH)nano-carrier with photothermal properties was synthesized by co-precipitation method,which loaded mesoporous silica coated nanoparticles connected with dihydroporphyphenol e6(Ce6)forming a nanocatalyst responding to acidic microenvironment of tumor(TME).In acid TME,FeMn-LDH degraded into Fe³⁺and Mn²⁺ions and initiated Fenton-like reaction for chemdynamic therapy(CDT).Furthermore,the generated heat upon near-infrared light irradiation further enhanced the CDT effect.At the same time,Fe³⁺can catalyze the decomposition of H₂O₂ to produce O₂,which enhances the O₂-dependent photodynamic therapy.Upconversion luminescence of UCNPs after FeMn-LDH decomposition also improved photodynamic therapy and imaging.Through rational construction,the as-built multifunctional platform could achieve an excellent anti-tumor efficiency.